Antibiotic Overuse Reduced Without Restricting Availability

Daniel M. Keller, PhD

September 27, 2011

September 27, 2011 (Chicago, Illinois) — A multidisciplinary antimicrobial stewardship program (ASP) at a tertiary-care hospital has reduced antibiotic use in that institution by one quarter. In addition, the use of simple innovative changes to prescribing practices reduced the development and transmission of multidrug resistant (MDR) organisms over a 3-year period.

The ASP was accompanied by a reduction in hospital costs and improvement in patient care.

A vital aspect of the ASP was not to restrict antibiotics, Kimberly Leuthner, PharmD, infectious disease clinical specialist at the University Medical Center of Southern Nevada in Las Vegas, reported here at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy.

Dr. Leuthner said that the overuse of antibiotics imposes selective pressure on bacteria, leading to MDR organisms. Elevated rates of MDR pathogens, high rates and long duration of therapy, and excessive expense within the medical center led staff in 2006 to implement a multidisciplinary ASP involving the infection control, microbiology, and pharmacy departments and functions.

The ASP included the evaluation of medication use for targeted drugs, a 10-day "stop protocol" for antimicrobial agents, expansion of a hospital-wide antibiogram, prevention strategies, and a continuing education program for nurses and physicians.

The ASP team decided not to restrict antibiotic prescribing, but to allow their use with education and de-escalation guidance. Drug use was monitored and was adjusted for patient census by expressing use as doses per 1000 patient-days.

Dr. Leuthner reported that antibiotic use decreased by 26.6%, and attributed the decrease to better compliance with medication use criteria and to the influence of the 10-day stop protocol. Stopping antimicrobial drugs sooner was associated with a significant decrease in the isolation of MDR pathogens (P = .02).

She said that through the efforts of the infection control department, isolates of Acinetobacter species, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) have decreased sharply (by 30.7%, 24.6%, and 25.5%, respectively). The budget for antimicrobial drugs dropped by approximately 40% over a 3-year period.

Session moderator Stephan Harbarth, MD, MS, associate professor, attending physician in infectious diseases, and associate hospital epidemiologist at Geneva University Hospitals in Switzerland, called the presentation "terrific" and "very courageous."

Dr. Harbarth said: "What they showed is that they overtreated common infections for extended durations of 16 to 21 days. What was the reason? They just had the wrong physician order entry system, which renewed automatically the antibiotic orders.... Of course, it's gross misconduct by the hospital to have this kind of automatic renewal of antibiotic orders."

Rather than automatic renewal of orders, the standard with the ASP is to have automatic stop orders to reduce the duration of antibiotic therapy.

Dr. Harbarth said that the hospital's resistance situation was a "nightmare," and that its antibiotic usage was "apocalyptic," with overuse of carbapenems, quinolones, and other classes.

Despite the progress that this particular medical center has made, Dr. Harbarth said that, based on what he heard in Dr. Leuthner's presentation, and compared with hospitals in Western Europe, it still has "huge overuse of antibiotics" and problems with Acinetobacter and MRSA. But he congratulated her for the progress made so far and for being "honest enough to report" the situation.

Dr. Harbarth emphasized to Medscape Medical News that an important part of an ASP is not to restrict the use of available antibiotics, because staff often shift to using other antibiotics, but often no more appropriately. "It's clear that in this setting, it wouldn't make sense to target specific agents if they are still allowed to use 16 to 21 days of antibiotics," he said.

In general, any ASP needs to be tailored for the specific setting, including intensive care, acute care, or long-term care, and to each facility. "It depends also on the country, on the epidemiology of resistance, on specific usage patterns; there is no 'one size fits all' antibiotic stewardship approach," Dr. Harbarth noted.

He pointed out some generally applicable principles that target the "low-hanging fruits" in many settings. "For instance, improved antibiotic prophylaxis, perioperative prophylaxis before patients go into surgery...[may lead to a] reduction of duration. [It] may be just providing some educational material that is not generic, but that is adapted to a specific institution, like providing them the antibiotic-resistance situation, providing them some pocket books with local guidelines," he advised.

Another essential aspect of an ASP is good diagnostic support, which he sees as a major problem in the United States. "Many microbiology labs have been outsourced. That means that even in large hospitals, you send it all across the United States.... If you don't get the results back quickly and you don't have direct contact with the microbiologists, sometimes you will have trouble narrowing the antibiotic treatment, and you may continue a broad-spectrum antibiotic," he warned.

He explained that Europe is ahead of the United States in the approval and availability of tools for the rapid identification of infections and causative pathogens. One such tool is matrix-assisted laser desorption/ionization – time-of-flight (MALDI-TOF) mass spectrometry.

"That really gives you a time gain — sometimes up to 2 days" — in identifying the bacterium and adapting antibiotic treatment appropriately, he said. "It's really revolutionizing clinical microbiology, at least in Europe."

Although MALDI-TOF mass spectrometry is an expensive technology to purchase, Dr. Harbarth emphasized that "the consumables are very cheap. It costs almost nothing to run."

Another advance is the measurement of serum procalcitonin as a biomarker of systemic infection. He said it is approved in the United States only for use in the intensive-care setting; in Western Europe, clinicians are using it to diagnose respiratory tract infections, "which may be also very useful for antibiotic stewardship."

The good negative predictive value of the test "has an anxiolytic effect on the prescriber," Dr. Harbarth said. "That means that it encourages him to withhold antibiotics. The second, even more important, advantage of this biomarker is that you can individualize treatment duration." About a dozen clinical trials support this point, showing that, in some cases, therapy could be reduced from an average of 10 days down to 6.

Finally, Dr. Harbarth advised colleagues to learn from each other, encouraging clinicians from the United States to visit hospitals outside of North America. He also foresees better practice with the use of computerized decision support tools and decreased diagnostic uncertainty with improved diagnostics.

He acknowledges the pressure on physicians in the United States to practice defensive medicine because of the threat of malpractice suits.

"Sometimes there's overuse of antibiotics because colleagues want to be on the safe side. If you go to some places in Denmark, in the Netherlands, in Germany, in Switzerland, people get amoxicillin for pneumonia, even when they come to the hospital," he said. "You wouldn't suggest this at a meeting here to colleagues in the United States."

Dr. Leuthner reports receiving speakers' fees from Cubist Pharmaceuticals and consulting fees as a scientific advisor to Forrest Pharmaceuticals. Dr. Harbarth has disclosed no relevant financial relationships.

51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract K-384. Presented September 17, 2011.

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